HNF-4α promotes multidrug resistance of gastric cancer cells through the modulation of cell apoptosis.

Multidrug resistance (MDR) typically leads to treatment failure, and is associated with disease progression of gastric cancer (GC). In the present study, a total of 15 aberrantly activated transcription factors (TFs) were detected in chemo-resistant GC cells using a TF Activation Profiling Plate Array. Among these TFs, hepatocyte nuclear factor (HNF)-4α was significantly upregulated in multidrug-resistant GC cells (P=0.019). The overexpression of HNF-4α was able to cause resistance to multiple chemotherapeutics, whereas inhibition of HNF-4α appeared to reverse cancer cell resistance. Further studies demonstrated that HNF-4α had no clear influence on drug transportation; however, inhibition of drug-induced cell apoptosis occurred as B-cell lymphoma 2 (Bcl-2) expression increased in GC cells. Additionally, immunohistochemistry demonstrated that HNF-4α was overexpressed in human GC tissues, and associated with tumor stage and lymph node metastasis. In conclusion, the results of the present study indicate the involvement of TFs in MDR in GC, and suggest that HNF-4α may enhance MDR in GC by regulating cell apoptosis and Bcl-2 expression.